“I go after Streptococcus pneumoniae and many other bacteria causing community-acquired pneumonia with vengeance but lately I have had a hard time keeping up with many gram-negatives, including some E. coli. Who am I?”

Additional hint: “The latest FDA warning against the use of my class of drugs has to do with increased risk of ruptures or tears in the aorta in certain patients, including the elderly and those with hypertension, aortic aneurysm or peripheral vascular disease.” 

Editor’s note: This post is part of the P4P “Talking Therapeutics” series designed to make learning about antibiotics fun. Individual antibiotics give a short description of themselves and you are asked to guess their names. Antimicrobial spectrum, common uses and potential adverse effects follow. Enjoy!

And the answer is…… HERE

Selected antimicrobial spectrum

                Gram-positives: Streptococcus pneumoniae, Staphylococcus aureus                         (some resistance even in MSSA), Enterococcus spp (urine;some resistance)

                Gram-negatives: Enterics (eg, E. coli, Klebsiella spp), Pseudomonas spp,                                 Stenotrophomonas maltophilia, H. influenzae, some ESBLs.

                 AVOID: MRSA, anaerobes

Common clinical uses: community-acquired pneumonia (CAP), healthcare-associated pneumonia (HAP), urinary tract infections (UTIs), legionnaire’s disease, abdominal infection (plus anaerobic coverage)

WATCH OUT! QT prolongation, C. difficile, central nervous system toxicity, seizures, myasthenia gravis, peripheral neuropathy, tendinopathy, drug interactions (eg. warfarin), and most recently aortic aneurysm diagnosis/dissection!

Remember the key features of levofloxacin before you prescribe it!

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Selected references

  1. FDA. FDA warns about increased risk of ruptures or tears in the aorta blood vessel with fluoroquinolone antibiotics in certain patients.  https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-increased-risk-ruptures-or-tears-aorta-blood-vessel-fluoroquinolone-antibiotics. Accessed Nov 26, 2020,.
  2. Marangon FB, Miller D, Muallem MS, et al. Ciprofloxacin and levofloxacin resistance among methicillin-sensitive Staphylococcus aureus isolates from keratitis and conjunctivitis. Am J Ophthal 2004;137:453-58. https://www.ajo.com/article/S0002-9394(03)01287-X/pdf
  3. Yasufuku T, Shigemura K, Shirakawa T, et al. Mechanisms of and risk factors for fluoroquinolone resistance in clinical Enterococcus faecalis from patients with urinary tract infections. J Clin Microbiol 2011;49:3912-16. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209098/
  4.  Rawla P, Helou MLE, Vellipuram AR. Fluoroquinolones and the risk of aortic aneurysm or aortic dissection: A systematic review and meta-analysis. Cardiovasc Hematol Agents Med Chem 2019;17:3-10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6865049/

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

“I go after Streptococcus pneumoniae and many other bacteria causing community-acquired pneumonia with vengeance but lately I have had a hard time keeping up with many gram-negatives, including some E. coli. Who am I?”

Should I routinely select antibiotics with activity against anaerobes in my patients with presumed aspiration pneumonia?

Anaerobes have been considered a major cause of aspiration pneumonia (AP) based on studies published in 1970’s (1-3). More recent data, however, suggest that anaerobes no longer play an important role in most cases of AP (4-7) and routine inclusion of specific anti-anaerobic drugs in their treatment is no longer necessary.

 
An important reason for anaerobes not playing an important role in AP in the current era is the change in the demographics of patients who may be affected. Patients reported in older studies often suffered from alcohol use disorder, drug ingestion, seizure disorders and acute cerebrovascular accident. In contrast, more recent data show that AP often occurs in nursing home residents, the elderly with cognitive impairment, and those with dysphagia, gastrointestinal dysmotility or tube feeding (8,9).

 
In addition, many cases of AP reported in older studies involved delay of 4 or more days before seeking medical attention and, not surprisingly, often presented with lung abscess, necrotizing pneumonia, empyema, or putrid sputum, features that are relatively rare in the current era.

 
Further supporting the diminishing role of anaerobes in AP, are recent microbiological studies of the respiratory tract in AP revealing the infrequent isolation of anaerobes and, even when isolated, often coexisting with aerobic bacteria. The latter observation is important because, due to the alteration in the redox potential (9,10), treatment of aerobic bacteria alone may lead to less oxygenation consumption and less favorable environment for survival of anaerobes in the respiratory tract.

 
We should also always consider the potential adverse effects of unnecessary antibiotics with anaerobic activity in our frequently debilitated patients, including gastrointestinal dysbiosis (associated with Clostridiodes difficile infections and overgrowth of antibiotic-resistant pathogens such as vancomycin-resistant enterococci (VRE), hypersensitivity reactions, drug interactions, and central nervous system toxicity (11,12).
Thus, the weight of the evidence does not justify routine anaerobic coverage of AP in today’s patients.

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References
1. Bartlett JG, Gorbach SL, Finegold SM. The bacteriology of aspiration pneumonia. Am J Med. 1974;56(2):202-7. https://www.ncbi.nlm.nih.gov/pubmed/4812076
2. Bartlett JG, Finegold SM. Anaerobic pleuropulmonary infections. Medicine (Baltimore). 1972;51(6):413-50. https://www.ncbi.nlm.nih.gov/pubmed/4564416
3. Bartlett JG, Gorbach SL. The triple threat of aspiration pneumonia. Chest. 1975;68(4):560-6. https://www.ncbi.nlm.nih.gov/pubmed/1175415
4. Finegold SM. Aspiration pneumonia. Rev Infect Dis. 1991;13 Suppl 9:S737-42. https://www.ncbi.nlm.nih.gov/pubmed/1925318
5. Bartlett JG. How important are anaerobic bacteria in aspiration pneumonia: when should they be treated and what is optimal therapy. Infect Dis Clin North Am. 2013;27(1):149-55. https://www.ncbi.nlm.nih.gov/pubmed/23398871
6. El-Solh AA, Pietrantoni C, Bhat A, Aquilina AT, Okada M, Grover V, et al. Microbiology of severe aspiration pneumonia in institutionalized elderly. Am J Respir Crit Care Med. 2003;167(12):1650-4. https://www.ncbi.nlm.nih.gov/pubmed/12689848
7. Marik PE, Careau P. The role of anaerobes in patients with ventilator-associated pneumonia and aspiration pneumonia: a prospective study. Chest. 1999;115(1):178-83. https://www.ncbi.nlm.nih.gov/pubmed/9925081
8. Bowerman TJ, Zhang J, Waite LM. Antibacterial treatment of aspiration pneumonia in older people: a systematic review. Clin Interv Aging. 2018;13:2201-13. https://www.ncbi.nlm.nih.gov/pubmed/30464429
9. Mandell LA, Niederman MS. Aspiration Pneumonia. N Engl J Med. 2019 Feb 14;380(7):651-663. doi: 10.1056/NEJMra1714562. https://www.ncbi.nlm.nih.gov/pubmed/30763196
10. Walden, W. C., & Hentges, D. J. (1975). Differential effects of oxygen and oxidation-reduction potential on the multiplication of three species of anaerobic intestinal bacteria. Applied microbiology, 30(5), 781–785. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC187272/
11. Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis. 2001;1(2):101-14. https://www.ncbi.nlm.nih.gov/pubmed/11871461
12. Bhalla A, Pultz NJ, Ray AJ, Hoyen CK, Eckstein EC, Donskey CJ. Antianaerobic antibiotic therapy promotes overgrowth of antibiotic-resistant, gram-negative bacilli and vancomycin-resistant enterococci in the stool of colonized patients. Infect Control Hosp Epidemiol. 2003;24(9):644-9. https://www.ncbi.nlm.nih.gov/pubmed/14510245

 

Contributed by Amar Vedamurthy, MD, MPH, Mass General Hospital, Boston, MA

Should I routinely select antibiotics with activity against anaerobes in my patients with presumed aspiration pneumonia?

Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?

Although there are many potential sources for Klebsiella sp. bacteremia, C. difficile infection (CDI) itself may be associated with GI translocation of enteric organisms.

A retrospective study of over 1300 patients found an incidence of 1.8% for CDI-associated bacteremia. E. coli, Klebsiella sp. , or Enterococcus sp. accounted for 72% of cases. History of malignancy, neutropenia (at the time of CDAD), and younger age (mean 59 y) were among the risk factors.1 Another study reported over 20 cases of bacteremia caused by C. difficile plus other bacteria often of enteric origin such the aforementioned organisms, Bacteroides sp, Candida sp, and Enterobacter sp.2

CDI is thought to predispose to bacterial translocation through the GI tract by alteration of mucosal indigenous microflora, overgrowth of certain pathogens, and presence of inflammation in the mucosa.3 Interestingly, C. difficile toxin A or B may play an active role in the bacterial adherence and penetration of the intestinal epithelial barrier.4  

Bonus pearl: Did you know that C. difficile may be found in the normal intestinal flora of 3% of healthy adults, 15-30% of hospitalized patients, and up to 50% of neonates? Why neonates seem immune to CDI is another fascinating story!

 

References

  1. Censullo A, Grein J, Madhusudhan M, et al. Bacteremia associated with Clostridium difficile colitis: incidence, risk factors, and outcomes. Open Forum Infectious Diseases, Volume 2, Issue suppl_1, 1 December 2015, 943, https://doi.org/10.1093/ofid/ofv133.659 https://academic.oup.com/ofid/article/2/suppl_1/943/2635179
  2. Kazanji N, Gjeorgjievski M, Yadav S, et al. Monomicrobial vs polymicrobial Clostridum difficile bacteremia: A case report and review of the literature. Am J Med 2015;128:e19-e26. https://www.amjmed.com/article/S0002-9343(15)00458-1/abstract
  3. Naaber P, Mikelsaar RH, Salminen S, et al. Bacterial translocation, intestinal microflora and morphological changes of intestinal mucosa in experimental models of Clostridium difficile infection. J Med Microbiol 1998; 47: 591-8. https://www.ncbi.nlm.nih.gov/pubmed/9839563 
  4. Clostridium difficile toxins may augment bacterial penetration of intestinal epithelium. Arch Surg 1999;134: 1235-1242. https://jamanetwork.com/journals/jamasurgery/fullarticle/390434
Why has my patient with Clostridium difficile diarrhea developed Klebsiella bacteremia?